Synthesis,characterization, fluorescence imaging,and cytotoxicity studies of a uracil‐based azo derivative and its metal complexes

A uracil‐based heterocyclic azo derivative was prepared by coupling diazotized 5‐aminouracil with 2‐naphthol. This ligand, viz., 1‐(2,4‐dioxopyrimidine‐5‐yl)‐azo‐naphth‐2‐ol (HNAP), was used as a precursor for the synthesis of a series of complexes with manganese(II), cobalt(II), nickel(II), copper(II), and zinc(II) ions. Various physicochemical measurements UV–Visible, Infrared (IR), ¹H NMR, ¹³C Nuclear Magnetic Resonance (NMR), and electron spin resonance (ESR) spectral studies were employed to characterize the ligand and the metal complexes. The ligand showed good selectivity toward Mn²⁺ over the other metal ions with a detection limit of 1.36 μM. This probe was used for the confocal fluorescence imaging of Mn²⁺ ions in Michigan Cancer Foundation‐7 (MCF‐7) cells. The ligand and the metal complexes were tested for their cytotoxicity on the MCF‐7 cell line. It was observed that complexation of HNAP with the metal ions exhibited a promising cytotoxicity.     

Reactions in Water – A Greener Approach Using Ruthenium Catalysts

Reactions using transition metals as catalysts have emerged as an efficient method in the recent times. However, the selection of solvent plays a crucial role in this regard. Several solvents used traditionally suffer majorly with problems of toxicity; high boiling point etc. leading to drastic reaction conditions. Water being a non‐toxic, non‐inflammable and environmentally benign can replace the hazardous organic solvents in laboratory as well as industry. Maintaining a minimum catalyst loading percentage we can advantageously avail high levels of selectivity. Water was found to be a good solvent medium for several metal catalysed reactions. An intramolecular deprotonation mechanism is followed by the ruthenium (II) catalysts in water; thereby, facilitating the catalytic action of the metal. These studies can help the industrial chemists to utilize water as a solvent for their reactions towards improvement of their waste management procedure. This review mainly focuses on the several recent developments in the above direction.     

Sources of electrical conductivity in SnO2

SnO2 is widely used as a transparent conductor and sensor material. Better understanding and control of its conductivity would enhance its performance in existing applications and enable new ones, such as in light emitters. Using density functional theory, we show that the conventional attribution of n-type conductivity to intrinsic point defects is incorrect. Unintentional incorporation of hydrogen provides a consistent explanation of experimental observations. Most importantly, we find that SnO2 offers excellent prospects for p-type doping by incorporation of acceptors on the Sn site. Specific strategies for optimizing acceptor incorporation are presented.     

Design and synthesis of fluorescent symmetric bis-triazolylated-1,4-dihydropyridines as potent antibreast cancer agents

Herein, we report the synthesis of fluorescent 1,4-dihydropyridine-linked bis-triazoles (2a–2n) through Hantzsch synthesis by the condensation of o/m-chloro-substituted benzaldehyde, ethyl 3-oxo-4(prop-2-yn-1-yloxy)butanoate, and ammonium acetate in the presence of Ba(NO₃)₂ as a catalyst followed by the click reaction of resultant Hantzsch product (1) with various aromatic as well as aliphatic azides. All the synthesized compounds were well characterized by ¹H-NMR, ¹³C-NMR, FTIR, and HRMS spectral techniques. Antibreast cancer evaluation of all the synthesized derivatives revealed that the compounds 2f (IC₅₀?=?7?±?0.02?µM) and 2g (IC₅₀?=?5?±?0.03?µM) showed better anticancer activity (lower IC₅₀) than the standard drug tamoxifen (IC₅₀?=?11.2?±?0.01?µM) against breast carcinoma (MDA-MB-231) cell line. The synthesized compounds were also screened against normal human embryonic kidney (HEK-293) cell line and found to be nontoxic. The fluorescent nature and cytotoxicity assay of these newly synthesized hybrids recommend their utility in tumor cell imaging.     

Studies towards iodine-catalyzed dehydrative-cycloisomerization of pent-4-yne-1,2-diols to di- and tri-substituted furans

An efficient and single-step iodine catalyzed and metal-free synthesis of di and tri-substituted 2-methylfuran derivatives were achieved from 1-popargyl-1,2-diols. Stereospecific synthesis of starting 1,2-diols was achieved by indium mediated Barbier type propargylation on corresponding keto-alcohols or by sodium borohydride mediated reduction of 2-hydroxy-2-propargyl ketones. The furan synthesis proceeded through iodine mediated 5-exo-trig cyclization, dehydration and reductive deiodination. The method was applied to the synthesis of 2-methylfuran fused to phenanthrene, pyrene and acenaphthylene rings.     

Benchmarking implicit solvent folding simulations of the amyloid beta(10-35) fragment

A pathogenetic feature of Alzhemier disease is the aggregation of monomeric beta-amyloid proteins (Abeta) to form oligomers. Usually these oligomers of long peptides aggregate on time scales of microseconds or longer, making computational studies using atomistic molecular dynamics models prohibitively expensive and making it essential to develop computational models that are cheaper and at the same time faithful to physical features of the process. We benchmark the ability of our implicit solvent model to describe equilibrium and dynamic properties of monomeric Abeta(10-35) using all-atom Langevin dynamics (LD) simulations, since Alphabeta(10-35) is the only fragment whose monomeric properties have been measured. The accuracy of the implicit solvent model is tested by comparing its predictions with experiment and with those from a new explicit water MD simulation, (performed using CHARMM and the TIP3P water model) which is approximately 200 times slower than the implicit water simulations. The dependence on force field is investigated by running multiple trajectories for Alphabeta(10-35) using the CHARMM, OPLS-aal, and GS-AMBER94 force fields, whereas the convergence to equilibrium is tested for each force field by beginning separate trajectories from the native NMR structure, a completely stretched structure, and from unfolded initial structures. The NMR order parameter, S2, is computed for each trajectory and is compared with experimental data to assess the best choice for treating aggregates of Alphabeta. The computed order parameters vary significantly with force field. Explicit and implicit solvent simulations using the CHARMM force fields display excellent agreement with each other and once again support the accuracy of the implicit solvent model. Alphabeta(10-35) exhibits great flexibility, consistent with experiment data for the monomer in solution, while maintaining a general strand-loop-strand motif with a solvent-exposed hydrophobic patch that is believed to be important for aggregation. Finally, equilibration of the peptide structure requires an implicit solvent LD simulation as long as 30 ns.     

Stress Degradation Behavior of Desipramine Hydrochloride and Development of Suitable Stability-Indicating LC Method

A simple reverse phase liquid chromatographic method was developed for the quantitative determination of desipramine hydrochloride and its related impurities in bulk drugs which is also stability-indicating. During the forced degradation at hydrolysis, oxidative, photolytic and thermal stressed conditions, the degradation results were only observed in the oxidative stress condition. The blend of the degradation product and potential impurities were used to optimize the method by an YMC Pack Pro C₁₈ stationary phase. The LC method employs a linear gradient elution with the water–acetonitrile–trifluoroacetic acid as mobile phase. The flow rate was 1.0 mL min^?1 and the detection wavelength 215 nm. The stressed samples were quantified against a qualified reference standard and the mass balance was found close to 99.0% (w/w) when the response of the degradant was considered to be equal to the analyte (i.e. desipramine). The developed RP-LC method was validated in agreement with ICH requirements.     

Exploitation of Catalytic Dyads by Short Peptide-Based Nanotubes for Enantioselective Covalent Catalysis

Extant enzymes with precisely arranged multiple residues in their three-dimensional binding pockets are capable of exhibiting remarkable stereoselectivity towards a racemic mixture of substrates. However, how early protein folds that possibly featured short peptide fragments facilitated enantioselective catalytic transformations important for the emergence of homochirality still remains an intriguing open question. Herein, enantioselective hydrolysis was shown by short peptide-based nanotubes that could exploit multiple solvent-exposed residues to create chiral binding grooves to covalently interact and subsequently hydrolyse one enantiomer preferentially from a racemic pool. Single or double-site chiral mutations led to opposite but diminished and even complete loss of enantioselectivities, suggesting the critical roles of the binding enthalpies from the precise localization of the active site residues, despite the short sequence lengths. This work underpins the enantioselective catalytic prowess of short peptide-based folds and argues their possible role in the emergence of homochiral chemical inventory.